PDZD9

Chr 16

PDZ domain containing 9

Also known as: C16orf65

NCBI Gene: 255762ENSG00000155714UniProt: Q8IXQ8

The protein functions as a scaffolding protein that organizes signaling complexes through its PDZ domains. Mutations cause autosomal recessive intellectual disability with variable features including developmental delay, seizures, and behavioral abnormalities. This gene shows low constraint against loss-of-function variants, and a GeneReviews entry is available for detailed clinical guidance.

GeneReviewsResearch
MultiplemechanismLOEUF 1.24
Clinical Summary— PDZD9
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
49 unique Pathogenic / Likely Pathogenic· 86 VUS of 200 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — PDZD9
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.24LOEUF
pLI 0.003
Z-score 1.09
OE 0.59 (0.31–1.24)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.83Z-score
OE missense 0.77 (0.64–0.93)
79 obs / 102.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.59 (0.31–1.24)
0≤0.351.4
Missense OE0.77 (0.64–0.93)
0≤0.61.4
Synonymous OE1.10
0≤1.21.6
LoF obs/exp: 5 / 8.4Missense obs/exp: 79 / 102.6Syn Z: -0.46
DN
0.74top 25%
GOF
0.73top 25%
LOF
0.3744th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic13
VUS86
Likely Benign35
Benign7
Conflicting3
36
Pathogenic
13
Likely Pathogenic
86
VUS
35
Likely Benign
7
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
34
0
36
Likely Pathogenic
1
0
12
0
13
VUS
2
53
31
0
86
Likely Benign
0
5
16
14
35
Benign
0
3
3
1
7
Conflicting
—3
Total3639615180

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PDZD9 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients